Biolchi Alessia, Tomei Sara, Brunelli Brunella, Giuliani Maria, Bambini Stefania, Borrow Ray, Claus Heike, Gorla Maria Cecilia O, Hong Eva, Lemos Ana Paula S, Lucidarme Jay, Taha Muhamed-Kheir, Vogel Ulrich, Budroni Sonia, Giuliani Marzia M, Rappuoli Rino, Boucher Philip, Pizza Mariagrazia
GSK, Siena, Italy.
Meningococcal Reference Unit, Public Health England, Manchester Royal Infirmary, Manchester, UK.
Infect Dis Ther. 2021 Mar;10(1):307-316. doi: 10.1007/s40121-020-00370-x. Epub 2020 Nov 13.
Invasive meningococcal disease (IMD) is an important public health concern. In developed countries, most IMD is caused by meningococcal serogroup B (MenB) and two protein-based MenB vaccines are currently available: the four-component vaccine 4CMenB (Bexsero, GSK) and the bivalent vaccine MenB-FHbp (Trumenba, Pfizer). Genes encoding the 4CMenB vaccine antigens are also present in strains belonging to other meningococcal serogroups.
To evaluate the potential of 4CMenB vaccination to protect adolescents against non-MenB IMD, we tested the bactericidal activity of sera from immunized adolescents on 147 (127 European and 20 Brazilian) non-MenB IMD isolates, with a serum bactericidal antibody assay using human complement (hSBA). Serum pools were prepared using samples from randomly selected participants in various clinical trials, pre- and post-vaccination: 12 adolescents who received two doses of 4CMenB 2 months apart, and 10 adolescents who received a single dose of a MenACWY conjugate vaccine (as positive control).
4CMenB pre-immune sera killed 7.5% of the 147 non-MenB isolates at hSBA titers ≥ 1:4. In total, 91 (61.9%) tested isolates were killed by post-dose 2 pooled sera at hSBA titers ≥ 1:4, corresponding to 44/80 (55.0%) MenC, 26/35 (74.3%) MenW, and 21/32 (65.6%) MenY isolates killed.
4CMenB vaccination in adolescents induces bactericidal killing of non-MenB isolates, suggesting that mass vaccination could impact IMD due to serogroups other than MenB.
侵袭性脑膜炎球菌病（IMD）是一个重要的公共卫生问题。在发达国家，大多数IMD由B群脑膜炎球菌（MenB）引起，目前有两种基于蛋白的MenB疫苗：四价疫苗4CMenB（Bexsero，葛兰素史克公司）和二价疫苗MenB-FHbp（Trumenba，辉瑞公司）。编码4CMenB疫苗抗原的基因也存在于属于其他脑膜炎球菌血清群的菌株中。
为了评估4CMenB疫苗接种对保护青少年免受非MenB IMD侵害的潜力，我们使用人补体血清杀菌抗体试验（hSBA），检测了免疫青少年血清对147株（127株欧洲菌株和20株巴西菌株）非MenB IMD分离株的杀菌活性。血清池是使用来自不同临床试验中随机选择的参与者在接种疫苗前后的样本制备的：12名青少年间隔2个月接种两剂4CMenB，10名青少年接种一剂A、C、W、Y群脑膜炎球菌结合疫苗（作为阳性对照）。
4CMenB免疫前血清在hSBA效价≥1:4时杀死了147株非MenB分离株中的7.5%。总共，91株（61.9%）检测的分离株在接种第二剂后血清池hSBA效价≥1:4时被杀死，其中包括44/80（55.0%）的C群脑膜炎球菌、26/35（74.3%）的W群脑膜炎球菌和21/32（65.6%）的Y群脑膜炎球菌分离株被杀死。
青少年接种4CMenB疫苗可诱导对非MenB分离株的杀菌作用，表明大规模接种可能会对除MenB血清群以外的其他血清群引起的IMD产生影响。
